title: Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway.
abstract: OBJECTIVE
  Swimming exercise leads to a nonpathological, physiological left ventricular hypertrophy. However, the potential molecular mechanisms are unknown. We investigated the role of microRNAs (miRNA) regulating the cardiac signal cascades were studied in exercised rats.
  
  
  METHODS
  Female Wistar rats were assigned into two groups: (1) sedentary control (SC), (2) swimming exercise (SE). The rats in the SE group completed a 1-h swimming exercise, 5 times/week/8-week with 5 % body overload. miRNA, phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3α), phosphatase and tensin homolog (PTEN) and tuberous sclerosis complex 2 (TSC2) gene expression analysis were performed by real-time PCR in heart muscle. Moreover, we assessed cardiac protein expression of ERK1/2, PI3K/AKT/mTOR, PTEN and TSC2.
  
  
  RESULTS
  Cardiac phospho(ser473)-AKT and phospho(Ser2448)-mTOR were, respectively, increased by 46 and 38 % in the SE group when compared with SC group. miRNAs-21, 144, and 145 were, respectively, up-regulated in the SE group (152 %, 128, and 101 % relative increases), but miRNA-124 was decreased by 38 %. In SE group, PIK3α (targeted by miRNA-124) gene expression increased by 213 %, and Pten (targeted by miRNAs-21 and 144), and TSC2 (targeted by miRNA-145) were, respectively, decreased by 51 and 55 %. In addition, the swimming exercise increased protein levels of PIK3α (36 %) and phospho(Thr1462)-TSC2 (48 %), while it decreased PTEN (37 %) and TSC2 (22 %), which induced activation of PI3K/AKT/mTOR signaling pathway.
  
  
  CONCLUSIONS
  These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, changing the expression of specific miRNAs targeting the PIK3/AKT/mTOR signaling pathway and its negative regulators.
authors.affiliation: Physical Education College, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Qi
authors.forename: Shuai
authors.initials: S
authors.lastname: Meng
authors.forename: Baoju
authors.initials: B
authors.lastname: Wen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D059267:Cardiomegaly, Exercise-Induced; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D005082:Physical Exertion; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013550:Swimming; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C000624655:Tsc2 protein, rat; C487216:Pten protein, rat